Rationale: The angiopoietins (Ang) comprise a family of growth factors mainly known for their role in blood vessel formation and remodelling. The best studied member, Ang-1, exhibits antiapoptotic and anti-inflammatory effects. Although the involvement of Ang-1 in angiogenesis is well-recognized, little information exists about its role in respiratory physiology and disease. Based on its ability to inhibit vascular permeability, adhesion molecule expression and cytokine production, we hypothesized that Ang-1 administration might exert a protective role in asthma. Objectives: To determine changes in the expression of Ang and to assess the ability of Ang-1 to prevent the histological, biochemical and functional changes observed in an animal model of asthma. Methods: To test our hypothesis a model of allergic airway disease that develops after ovalbumin(OVA) sensitization and challenge was used. Measurements and Main results: Ang-1 expression was reduced at the mRNA and protein levels in lung tissue of mice sensitized and challenged with ovalbumin leading to reduced Tie2 phoshporylation. Intranasal Ang-1 treatment prevented the ovalbumin-induced eosinophilic lung infiltration, attenuated the increase in IL-5 and IL-13 and reduced eotaxin and VCAM-1 expression. These anti-inflammatory actions of Ang-1 coincided with higher levels of IB and decreased NF-B binding activity. More importantly, Ang-1 reversed the ovalbumin-induced increase in tissue resistance and elastance, improving lung function. Conclusions: We conclude that Ang-1 levels are decreased in asthma and that administration of Ang-1 might be of therapeutic value as it prevents the increased responsiveness of the airways to constrictors and ameliorates inflammation.